Tian Sheng Memorial Hospital

Taiwan, Taiwan

Tian Sheng Memorial Hospital

Taiwan, Taiwan
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Su C.-C.,Tian Sheng Memorial Hospital | Liu Y.-F.,Chung Shan Medical University | Li S.-Y.,Chung Shan Medical University | Yang J.-J.,Chung Shan Medical University | Yen Y.-C.,Chi Mei Medical Center
Eye (Basingstoke) | Year: 2012

PurposeGlaucoma is one of the leading causes of blindness in the world. Juvenile-onset open-angle is a subtype of glaucoma. In this context, we investigate the possible mutations in the promoter and coding regions of the CYP1B1 gene among patients suffering juvenile-onset open-angle glaucoma (JOAG).MethodsThe CYP1B1 gene was analysed for mutations in 61 unrelated Taiwanese probands with JOAG and in 100 healthy control subjects. Genomic DNA was extracted from peripheral blood leukocytes and then subjected to PCR. The amplified products were screened for base mutations by autosequence. Next, data from the two groups were compared using the χ 2 test. Additionally, three-dimensional (3D) modelling of the human wild-type and p.R390H mutation was performed using SWISS-MODEL, an automated homology modelling program. Finally, the figure was prepared for the modelled structures by using the Accelrys ViewerLite 5.0 program.ResultsAnalysis results indicated two CYP1B1 mutations and five polymorphisms. The prevalence of CYP1B1 gene mutations in this study was 4.92% (3/61). The mutations included a missense mutation (p.Arg390His; 2/3) and a mutation in the 5′-untranslated region (c.1-313A>C; 1/3). Moreover, computer-assisted modelling revealed that this p.R390H mutation affects the intra-molecular interaction in the hydrogen-bonding interaction with Glu387 and Asn428, thus altering significantly the efficiency of the haem-binding and proper folding of the molecule.ConclusionsAs a result, the p.Arg390His mutation might affect the protein structure and, ultimately, the normal function of CYP1B1. Therefore, we suggest that the c.1169G>A (p.Arg390His) mutation of CYP1B1 may be a risk factor for the development of JOAG. © 2012 Macmillan Publishers Limited All rights reserved.


Lin M.-Y.,Tian Sheng Memorial Hospital | Lin S.-J.,Kaohsiung Medical University | Chan L.-C.,Tian Sheng Memorial Hospital | Lu Y.-C.,Tian Sheng Memorial Hospital
International Journal of Tuberculosis and Lung Disease | Year: 2010

OBJECTIVE: To compare the effects of food and antacids on the bioavailability of first-line anti-tuberculosis drugs. METHOD: Systematic search of electronic databases PubMed (January 1950-May 2009), and the Cochrane Library database (January 1974-May 2009), including the Cochrane Centre register of controlled trials, and ongoing trials from research registers using key terms 'food', 'antacids', 'meal', 'controlled trial', 'diet', and the fi rst-line anti-tuberculosis drugs isoniazid (INH), rifampicin (RMP), ethambutol (EMB) and pyrazinamide (PZA). Meta-analysis was performed using RevMan software 5 to assess the impact of food or antacids on the maximum plasma concentrations (Cmax) and area under the plasma concentration time curve (AUC) of anti-tuberculosis drugs. RESULTS: Twelve trials involving 157 patients were included in the meta-analysis. The overall effects showed that food signifi cantly reduced the Cmax mean difference (Cmax MD; Cmax MD -1.42, 95%CI -1.56-1.28, P < 0.00001) and AUC (Cmax MD -3.33, 95%CI -4.05-2.62, P < 0.00001) of INH but antacids did not. Food also signifi cantly reduced the Cmax MD (Cmax MD -2.47, 95%CI -3.30-1.64, P < 0.00001) but not the AUC of RMP. Antacids had no effect on the Cmax MD or AUC of RMP. The Cmax and AUC of PZA were unaffected by both food and antacids. Both food and antacids reduced the Cmax but not the AUC of EMB. CONCLUSION: From a pharmacokinetic point of view, it seems that the better option for patients with gastrointestinal upsets during chemotherapy would be to add antacids rather than dosing with meals. © 2010 The Union.


Liu J.-Y.,China Medical University at Taichung | Lee M.-J.,Tian Sheng Memorial Hospital | Chen H.-M.,Fu Jen Catholic University | Tzang B.-S.,Chung Shan Medical University | And 3 more authors.
Evidence-based Complementary and Alternative Medicine | Year: 2011

Increased cell death of cardiomyocyte by oxidative stress is known to cause dysfunction of the heart. O. gratissimum is one of the more well-known medicinal plants among the Ocimum species and widely used in treatment of inflammatory diseases. In this study, we hypothesized that aqueous extract of O. gratissimum leaf (OGE) may protect myocardiac cell H9c2 from oxidative injury by hydrogen peroxide (H2O2). Our results revealed that OGE pretreatment dose-dependently protects H9c2 cells from cell death when exposed to H2O2. Additionally, DNA condensation induced by H 2O2 was also reduced by OGE pretreatment, suggesting that Ocimum gratissimum extract may attenuate H2O2-induced chromosome damage. Further investigation showed that OGE pretreatment inhibited H2O2-induced activation of caspase-3 and caspase-9, as well as H2O2-induced upregulation of proapoptotic Apaf-1 and the release of cytosolic cytochrome c, but has little effect on the activation of caspase-8. Additionally, OGE pretreatment significantly upregulated Bcl-2 expression and Akt phosphorylation, and slightly affected the phosphorylation of mitogen-activated protein kinases including p38 MAPK and JNK. Taken together, our findings revealed that Ocimum gratissimum extract effectively inhibited the mitochondrial pathway and upregulated Bcl-2 expression, which may be important in protecting H9c2 cells from H 2O2-induced cell death.


Wang C.-H.,Kaohsiung Medical University | Wang C.-H.,Tian Sheng Memorial Hospital | Leung M.,Kaohsiung Municipal United Hospital | Liang W.-C.,Kaohsiung Medical University | And 3 more authors.
Neuromuscular Disorders | Year: 2012

This study aimed to evaluate muscle involvement pattern and correlate the lesions on muscle imaging with clinical features and D4Z4 fragment size in 24 patients with facioscapulohumeral muscular dystrophy (FSHD). The grading of the muscle image detected by computed tomography (CT) was based on a four-point semi-quantitative visual scale. On muscle CT, the most affected muscle was trapezium, followed by hamstrings. CT image identified hamstrings involvement rather than shoulder-girdle in clinically asymptomatic subjects. CT image also showed that axial muscle was affected in one-third of patients which appeared even earlier than clinical manifestation. Strong correlations between CT findings, serum creatine kinase level and clinical severity scores were also found. Asymmetric involvement was more evident on CT image than it identified in manual muscle strength testing. Inverse correlation between CT grade and D4Z4 fragment size was clearly demonstrated. These findings suggest muscle CT will be helpful for the process of early intervention in FSHD, even in subjects in a preclinical status. © 2011 Elsevier B.V.


Li C.-S.,Tian Sheng Memorial Hospital | Schminke U.,University of Greifswald | Tan T.-Y.,Chang Gung University
Clinical Neurology and Neurosurgery | Year: 2010

Objective: Irradiation induced extracranial carotid occlusive disease has been recognized as a potential cause of post-irradiation stroke in nasopharyngeal carcinoma (NPC) patients. Our study aims to investigate the prevalence of extracranial CA disease in post-irradiated Taiwanese NPC ischemic stroke patients. Methods: Forty-threeNPCpatients with ischemic stroke were retrospectively selected from the stroke registration of the study hospital and compared with 276 first-ever ischemic stroke patients from the same database, of which 31 patients underwent carotid duplex sonography (CDS). Significant atherosclerotic lesions of the carotid arteries were defined as a >50% stenosis or an occlusion according to CDS. Results: Significant carotid lesions occurred in 13 of 31 (42%) NPC patients. Stroke was more frequently caused by large artery disease (44% versus 23%; p < 0.01) in NPC patients than in first-ever stroke patients without NPC. Carotid artery disease (odds ratio 7.22, 95% confidence interval 2.51-20.77; p < 0.0001) and absence of diabetes mellitus (odds ratio 0.26, 95% confidence interval 0.07-0.93; p = 0.039) were the strongest independent discriminators between NPC stroke patients and non-NPC stroke patients in a multivariate logistic regression analysis. Conclusion: Patients who received neck irradiation are at risk for the delayed development of diffused atherosclerosis but also for carotid occlusion within years, although the mechanism remains elusive and probably multifactorial. © 2010 Elsevier B.V. All rights reserved.


Wang W.-H.,Chang Gung University | Liu Y.-F.,Chung Shan Medical University | Su C.-C.,Tian Sheng Memorial Hospital | Su M.-C.,Chung Shan Medical University | And 2 more authors.
PLoS ONE | Year: 2011

Dysfunctional gap junctions caused by GJB2 (CX26) and GJB6 (CX30) mutations are implicated in nearly half of nonsyndromic hearing loss cases. A recent study identified a heterozygous mutation, c.119C>T (p.A40V), in the GJB6 gene of patients with nonsyndromic hearing loss. However, the functional role of the mutation in hearing loss remains unclear. In this study, analyses of cell biology indicated that a p.A40V missense mutation of CX30 causes CX30 protein accumulation in the Golgi body rather than in the cytoplasmic membrane. The tet-on protein expression system was used for further study of mutant proteins in CX30 and CX30A40V co-expressions and in CX26 and CX30A40V co-expressions. The p.A40V missense mutation exerted a dominant negative effect on both normal CX30 and CX26, which impaired gap junction formation. Moreover, computer-assisted modeling suggested that this p.A40V mutation affects the intra molecular interaction in the hydrophobic core of Trp44, which significantly alters the efficiency of gap junction formation. These findings suggest that the p.A40V mutation in CX30 causes autosomal-dominant nonsyndromic hearing loss. These data provide a novel molecular explanation for the role of GJB6 in hearing loss. © 2011 Wang et al.


Su T.-R.,Tian Sheng Memorial Hospital | Zei W.-S.,Chung Shan Medical University | Su C.-C.,Tian Sheng Memorial Hospital | Hsiao G.,Taipei Medical University | Lin M.-J.,Chung Shan Medical University
Evidence-based Complementary and Alternative Medicine | Year: 2012

The purpose of this study was to investigate the effect of KCNQ (potassium channel, voltage-gated, KQT-like subfamily) openers in preventing myotonia caused by anthracene-9-carboxylic acid (9-AC, a chloride channel blocker). An animal model of myotonia can be elicited in murine skeletal muscle by 9-AC treatment. KCNQ openers, such as retigabine and flupirtine, can inhibit the increased twitch amplitude (0.1Hz stimulation) and reduce the tetanic fade (20Hz stimulations) observed in the presence of 9-AC. Furthermore, the prolonged twitch duration of skeletal muscle was also inhibited by retigabine or flupirtine. Lamotrigine (an anticonvulsant drug) has a lesser effect on the muscle twitch amplitude, tetanic fade, and prolonged twitch duration as compared with KCNQ openers. In experiments using intracellular recordings, retigabine and flupirtine clearly reduced the firing frequencies of repetitive action potentials induced by 9-AC. These data suggested that KCNQ openers prevent the myotonia induced by 9-AC, at least partly through enhancing potassium conductance in skeletal muscle. Taken together, these results indicate that KCNQ openers are potential alternative therapeutic agents for the treatment of myotonia. Copyright © 2012 Tzu-Rong Su et al.


Liang W.-G.,Chung Shan Medical University | Liang W.-G.,National Tsing Hua University | Su C.-C.,Tian Sheng Memorial Hospital | Nian J.-H.,Chung Shan Medical University | And 3 more authors.
Cell Biochemistry and Biophysics | Year: 2011

Gap junctional intercellular communication has numerous functions, each of which meets the particular needs of organs, tissues, or groups of cells. Connexins (CXs) are homologous four-transmembrane-domain proteins that are the major components of gap junctions. CX30. 2/CX31. 3 (GJC3) is a relatively new member of the CX protein family. Until now, however, the functional characteristics of CX30. 2/CX31. 3 have been unclear. To elucidate the properties of CX30. 2/CX31. 3 channels, their subcellular localization in HeLa cells, their effectiveness in dye transfer, and function on channels were investigated. In the immunofluorescent assay, cells that express CX30. 2/CX31. 3-GFP exhibited continuous fluorescence along the apposed cell membranes, rather than punctated fluorescence in contacting membranes between two cells. Surprisingly, dyes that can be capable of being permeated by CX26 GJ, according to a scrape loading dye transfer assay in previous studies, are impermeated by CX30. 2/CX31. 3 GJ, suggesting a difference between the characteristics of CX30. 2/CX31. 3 GJ and CX26 GJ. Furthermore, a significant amount of ATP was released from the HeLa cells that stably expressed CX30. 2/CX31. 3, in a medium with low calcium ion concentration, suggesting a hemichannel-based function for CX30. 2/CX31. 3. Based on these findings, we suggest that CX30. 2/CX31. 3 shares functional properties with pannexin (hemi) channels rather than gap junction channels of other CXs. © 2011 Springer Science+Business Media, LLC.


Su C.-C.,Tian Sheng Memorial Hospital | Li S.-Y.,Chung Shan Medical University | Su M.-C.,Chung Shan Medical University | Chen W.-C.,Chung Shan Medical University | Yang J.-J.,Chung Shan Medical University
European Journal of Human Genetics | Year: 2010

Hearing impairment is the most common sensory disorder worldwide. In a recent study, the authors have shown that a heterozygous missense mutation, p.R184Q, in the connexin 26 (Cx26) is causally related to hearing loss. However, the functional change in the Cx26R184Q mutant remains unknown. This study compared the intracellular distribution and assembly of mutant Cx26R184Q with that of the wild-type (WT) Cx26 and Cx30WT in tet-on HeLa cells and the effect that the mutant protein had on those cells. Fluorescent localization assay of WT Cx26 showed the typical punctuate pattern of gap junction channel between neighboring expression cells. Conversely, the p.R184Q missense mutation resulted in accumulation of the Cx26 mutant protein in the Golgi apparatus rather than in the cytoplasmic membrane. Cx26R184Q coexpressed with either Cx26WT or Cx30WT showed perinuclear localization by bidirectional tet-on expression system, suggesting the impairment of the ability of both WT proteins to intracellular trafficking and targeting to the plasma membrane. Therefore, we proposed that Cx26R184Q has a dominant-negative effect on the function of WT Cx26 and Cx30. © 2010 Macmillan Publishers Limited All rights reserved.


Hong H.-M.,Chung Shan Medical University | Yang J.-J.,Chung Shan Medical University | Su C.-C.,Tian Sheng Memorial Hospital | Chang J.-Y.,Chung Shan Medical University | And 2 more authors.
Human Genetics | Year: 2010

Connexins (Cxs) are homologous four-transmembrane domain proteins and constitute the major components of gap junctions. Among a cohort of patients with nonsyndromic hearing loss, we recently identified a novel missense mutation, E269D, in the GJC3 gene encoding connexin 29 (Cx29), as being causally related to hearing loss. The functional alteration of Cx29 caused by the mutant GJC3 gene, however, remains unknown. This study compared the intracellular distribution and assembly of mutant Cx29 (Cx29E269D) with that of the wild-type Cx29 (Cx29WT) in HeLa cells and the effect the mutant protein had on those cells. Cx29TW showed continuous staining along apposed cell membranes in the fluorescent localization assay. In contrast, the p.E269D missense mutation resulted in accumulation of the Cx29 mutant protein in the endoplasmic reticulum (ER) rather than in the cytoplasmic membrane. Co-expression of Cx29WT and Cx29E269D proteins by a bi-directional tet-on expression system demonstrated that the heteromeric connexon accumulated in the cytoplasm, thereby impairing the formation of the gap junction. Based on these findings, we suggest that Cx29E269D has a dominant negative effect on the formation and function of the gap junction. These results provide a novel molecular explanation for the role Cx29 plays in the development of hearing loss. © 2009 Springer-Verlag.

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